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© The Rockefeller University Press, 0021-9525/2000//1445 $5.00
The Journal of Cell Biology, Volume 150, Number 6, , 2000 1445-1460

Expression and Function of _vβ₃ and _vβ₅ Integrins in the Developing Pancreas

Vincenzo Cirulli^a, Gillian M. Beattie^a, George Klier^d, Mark Ellisman^b, Camillo Ricordi^c, Vito Quaranta^d, Francine Frasier^d, Jennifer K. Ishii^e, Alberto Hayek^a, and Daniel R. Salomon^e

^a The Islet Research Laboratory at The Whittier Institute for Diabetes, Department of Pediatrics
^b The National Center for Microscopy and Imaging Research, University of California San Diego, La Jolla, California 92037
^c The Diabetes Research Institute, University of Miami School of Medicine, Miami, Florida 33136
^d Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037
^e Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037

Cell–cell and cell–matrix interactions play a critical role in tissue morphogenesis and in homeostasis of adult tissues. The integrin family of adhesion receptors regulates cellular interactions with the extracellular matrix, which provides three-dimensional information for tissue organization. It is currently thought that pancreatic islet cells develop from undifferentiated progenitors residing within the ductal epithelium of the fetal pancreas. This process involves cell budding from the duct, migration into the surrounding mesenchyme, differentiation, and clustering into the highly organized islet of Langerhans. Here we report that _vβ₃ and _vβ₅, two integrins known to coordinate epithelial cell adhesion and movement, are expressed in pancreatic ductal cells and clusters of undifferentiated cells emerging from the ductal epithelium. We show that expression and function of _vβ₃ and _vβ₅ integrins are developmentally regulated during pancreatic islet ontogeny, and mediate adhesion and migration of putative endocrine progenitor cells both in vitro and in vivo in a model of pancreatic islet development. Moreover, we demonstrate the expression of fibronectin and collagen IV in the basal membrane of pancreatic ducts and of cell clusters budding from the ductal epithelium. Conversely, expression of vitronectin marks a population of epithelial cells adjacent to, or emerging from, pancreatic ducts. Thus, these data provide the first evidence for the contribution of integrins _vβ₃ and _vβ₅ and their ligands to morphogenetic events in the human endocrine pancreas.

Key Words: pancreatic islets • endocrine progenitors • _vβ₃ • integrins • cell migration

© 2000 The Rockefeller University Press

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